The overall objective of the project is to examine the biophysical and biochemical properties of the processes involved in the active secretion of electrolytes and water by the small intestine and to determine the effects on these processes of bacterial and viral enterotoxins, especially cholera toxin. Included in this overall objective are the following more precise objectives: (1)a formal description of the active ion transport processes of the small intestine that contribute to net absorption or secretion of solute, including an understanding of the extent of coupling between processes, the effects of changes in the ionic composition of the bathing medium, the effects of hormones and pharmacologic agents and the anatomic localization of processes with respect to cell type (crypt or villus) and cell border (luminal or basolateral); (2) a study of the biochemical factors involved in the regulation of these ion transport processes, principally the adenyl cyclase system, its regulation and its anatomic localization within the epithelium but also the guanyl cyclase system and the Na, K, ATPase system; (3) a study of the mechanism by which cholera toxin activates intestinal mucosal adenyl cyclase, including a search for factors that modify this interaction; and (4) a study of other enterotoxins (i.e. E. Coli, Chlostridium perfringens, Staphlococcal, Shigella), particularly those that affect adenyl cyclase.